Direct MRI mapping of neuronal magnetic fields in the human brain Functional MRI technique has greatly enhanced our understanding of the functional organization of the human brain. Currently used fMRI techniques, however, depend on measuring regional cerebral hemodynamics to infer neural activation, rather than detecting neuronal activity directly. This indirect measurement has several limitations. First, regional cerebral hemodynamics does not necessarily always reflect neuronal activity and could change (for example, drug effects) without underlying neuronal activity change. Second, vascular geometry may not always overlap with the area of neural firing, so that the mediation of regional cerebral hemodynamics may degrade spatial localization. Third, the cerebral hemodynamics responses are much slower (seconds) than neuronal firing (milliseconds). Temporal resolution of the hemodynamic measurement is, therefore, limited and downgraded with respect to the underlying neural activation. To address shortcomings of current fMRI techniques, we reported a novel fMRI technique, magnetic source MRI (msMRI), for directly assessing neuronal function at 2003. The technique is based on directly detecting MRI signal changes in response to the changes in magnetic fields concomitant with neuronal firing and offers improved spatial localization and temporal resolution. While it offers promise, msMRI is still at its early developmental stage. Controversial results have been reported. The overall objectives of this developmental proposal are then to study mechanisms of signal contrast in msMRI and to clarify the controversies. Theoretical modeling will be performed to study mechanisms of msMRI and characteristic spatial and temporal signatures of msMRI signals (Aim1). The characteristic temporal signature of msMRI signals will be investigated by demonstrating that msMRI has high temporal resolution and can accurately detect the timing of both stimulation onset and offset (Aim2). Characteristic spatial signatures of msMRI signal will be investigated by demonstrating unique and different spatial distributions for phase and magnitude images (Aim3). Unique relationships between msMRI signals and experimental parameters will be explored (Aim4). Finally, the distinct sensitivity of msMRI signals to a symmetry SE sequence will be investigated (Aim5). Successful completion of the current project will enhance our understanding of mechanisms of signal contrast in msMRI;clarify the controversy surrounding msMRI detections;and provide a solid background for future developments, optimizations, and applications of the msMRI technique. PUBLIC HEALTH RELEVANCE: The overall objectives of this developmental proposal are to study mechanisms of signal contrast in magnetic source magnetic resonance imaging (msMRI) and to develop msMRI procedures for mapping human brain functions. Successful completion of the current project will enhance our understanding of mechanisms of signal contrast in msMRI;clarify the controversy surrounding msMRI detections;and provide a solid background for future developments, optimizations, and applications of the msMRI technique